Project Summary Primary progressive aphasia (PPA) is a progressive neurological disorder that causes a gradual decline in communication ability as a result of selective neurodegeneration of speech and language networks in the brain. PPA is a devastating condition affecting adults as young as their 50?s, depriving them of the ability to communicate and function in society. There has been significant progress in discovering the neurobiological mechanisms that underlie PPA and in identifying its clinical phenotypes. With these advances, we are poised to investigate behavioral treatments that are grounded in modern cognitive and neuroanatomical concepts. Research documenting the efficacy of speech-language treatment for PPA is emerging, but limited. Systematic research is needed to establish best clinical practices in this unique patient population for whom pharmacological treatment remains elusive. The long-term objectives of this project are to provide evidence- based treatment methods addressing the speech and language deficits in PPA and to determine the neural predictors of responsiveness to intervention. The study has three main goals that build on the findings of our previous work: 1) to examine the utility of treatments designed to facilitate significant, generalized and lasting improvement of speech-language function in PPA, 2) to determine whether treatment alters the trajectory of decline in PPA by comparing performance on primary outcome measures in treated versus untreated participants after a one-year interval, and 3) to identify imaging predictors (gray matter, white matter, and functional connectivity measures) of responsiveness to behavioral intervention in individuals with PPA. In order to accomplish these aims, we will enroll 60 individuals with PPA, who will undergo a comprehensive multidisciplinary evaluation and neuroimaging. Subsequently, participants will be enrolled in treatment designed to promote lasting and generalized improvement of communicative function in core speech-language domains. Participants will be followed for up to one year post-treatment in order to determine long-term effects of rehabilitation, and their performance will be compared with a historical cohort of untreated PPA patients. This ambitious study and the necessary recruitment will be possible due to an ongoing collaboration with the UCSF Memory and Aging Center, a leading institution in the field of PPA research. The study will broaden the evidence base supporting the efficacy of speech-language intervention in PPA and will provide novel evidence regarding neural predictors of treatment outcomes, with the potential to inform clinical decision-making and improve clinical care for individuals with this debilitating disorder.